Cytokinesis is controlled by monomer-dimer switching of survivin

Abstract

Defects in chromosome or cytoplasm segregation during cell division can lead to aneuploidy, genomic instability, and cellular abnormalities, which are associated with dysregulation of key players of the cell cycle or even disturbances of their network interactions. Survivin and myosin-II binding are essential for proper cell cycle progression, maintaining cleavage furrow ingression, and cytokinesis. The timing and position of this interaction are marked by the dephosphorylation and dimerisation state of survivin. The ser/thr kinase family is involved in the phosphorylation state of both proteins. Tank-binding kinase 1 (TBK1) has recently been implicated in regulating mitotic progression and cytokinesis, however, its precise roles in this process are still being elucidated. This study shows, for the first time, the impact of phosphorylation of survivin at an N-terminal located threonine (thr5) in its interaction with itself and myosin-II. It provides evidence that expression of T5E, a phosphomimic, reduces interaction and causes myosin-II to mislocalise without impacting localisation of survivin. It shows that SVN T5E disrupts the cytokinesis process and forms binucleated cells, similar to monomeric survivin results. The research also establishes a survivin bimolecular fluorescence complementation platform system to provide further analysis of the mitotic function of survivin. Moreover, in vivo techniques between survivin and TBK1 detect an interaction between them, and this interaction is at its highest during late mitosis. The study further shows that phosphorylation of TBK1 at ser172 in Hela cells is required for proper survivin localisation at the centromere and midbody. These findings provide promising data to support that TBK1 acts as a kinase regulator of survivin, switching the monomer-dimer state and indirectly regulating its function during mitosis.